Refrigerator-temperature stable influenza vaccine compositions
Methods and compositions for the optimization and production of refrigerator-temperature stable virus, e.g., influenza, compositions are provided. Formulations and immunogenic compositions comprising refrigerator-temperature stable virus compositions are provided.
1. A refrigerator-stable live cold-adapted influenza virus composition which comprises at least one strain of influenza virus and further comprises a stabilizer consisting of:
(a) 2% to 8% sucrose weight/volume (w/v), 0.75% to 2% arginine w/v, 0.02% to 0.15% glutamate w/v, 0.05% to 2% gelatin hydrolysate, and a buffer; or
(b) 2% to 8% sucrose w/v, 0.75% to 2% arginine w/v, 0.05% to 2% gelatin hydrolysate, and a buffer;
wherein each amount of each of the components of the stabilizer is the final amount in the virus composition, and which virus composition exhibits a potency loss of less than 1.0 log over a 12 month period when stored at 4° C. to 8° C.
2. The refrigerator-stable live cold-adapted influenza virus composition of claim 1 , wherein at least one influenza virus strain is selected from: an attenuated cold-adapted influenza virus, a temperature-sensitive cold-adapted influenza virus, and an attenuated cold-adapted temperature-sensitive influenza virus.
3. The refrigerator-stable live cold-adapted influenza virus composition of claim 1 , wherein at least one influenza virus strain comprises a genetic backbone of ca A/Ann Arbor/6/60 or ca B/Ann Arbor/1/66.
4. The refrigerator-stable live cold-adapted influenza virus composition of claim 1 , wherein the stabilizer consists of 6.84% sucrose w/v, 1.21% arginine w/v, 0.094% glutamate w/v, 1% gelatin hydrolysate, and a buffer.
5. The refrigerator-stable live cold-adapted influenza virus composition of claim 1 , wherein the stabilizer consists of 6.84% sucrose w/v, 1.21 arginine w/v, 1% gelatin hydrolysate, and a buffer.
6. The refrigerator-stable live cold-adapted influenza virus composition of claim 1 , wherein the buffer is a potassium phosphate buffer.
7. The refrigerator-stable live cold-adapted influenza virus composition of claim 4 , wherein the buffer is a potassium phosphate buffer.
8. The refrigerator-stable live cold-adapted influenza virus composition of claim 6 , wherein the potassium phosphate buffer comprises 1.13% (w/v) dibasic potassium phosphate and 0.48% (w/v) monobasic potassium phosphate.
9. The refrigerator-stable live cold-adapted influenza virus composition of claim 7 , wherein the potassium phosphate buffer comprises 1.13% (w/v) dibasic potassium phosphate and 0.48% (w/v) monobasic potassium phosphate.
10. The refrigerator-stable live cold-adapted influenza virus composition of claim 1 , wherein the arginine is arginine monohydrochloride and the glutamate is glutamic acid monosodium monohydrate.
11. The refrigerator-stable live cold-adapted influenza virus composition of claim 4 , wherein the arginine is arginine monohydrochloride and the glutamate is glutamic acid monosodium monohydrate.
12. The refrigerator-stable live cold-adapted influenza virus composition of claim 1 , wherein a vaccine formulation of the composition comprises between 6.5 to 7.5 log 10 fluorescent focus units (FFU) of each influenza virus strain per 0.2 mL dose.
13. The refrigerator-stable live cold-adapted influenza virus composition of claim 4 , wherein a vaccine formulation of the composition comprises between 6.5 to 7.5 log 10 fluorescent focus units (FFU) of each influenza virus strain per 0.2 mL dose.
14. The refrigerator-stable live cold-adapted influenza virus composition of claim 1 , wherein the composition comprises at least two influenza virus strains.
15. The refrigerator-stable live cold-adapted influenza virus composition of claim 14 , wherein the composition comprises three influenza virus strains.
16. An immunogenic composition comprising the refrigerator-stable live cold-adapted influenza virus composition of claim 1 .
17. A vaccine comprising the immunogenic composition of claim 16 .
18. A refrigerator-stable live cold-adapted influenza virus vaccine formulation which comprises:
a) at least two strains of influenza virus, wherein:
i) at least one influenza virus strain comprises a genetic backbone of ca A/Ann Arbor/6/60 and at least one influenza virus strain comprises a genetic backbone of ca B/Ann Arbor/1/66, and
ii) the vaccine formulation comprises between 6.5 to 7.5 log 10 fluorescent focus units (FFU) of each influenza virus strain per 0.2 mL dose; and
b) a stabilizer consisting of 6.84% sucrose w/v, 1.21% arginine monohydrochloride w/v, 0.094% glutamic acid monosodium monohydrate w/v, 1% gelatin hydrolysate, and a potassium phosphate buffer, which buffer comprises 1.13% (w/v) dibasic potassium phosphate and 0.48% (w/v) monobasic potassium phosphate;
wherein each amount of each of the components of the stabilizer is the final amount in the vaccine formulation, and which vaccine formulation exhibits a potency loss of less than 1.0 log over a 12 month period when stored at 4° C. to 8° C.
19. The vaccine formulation of claim 18 , wherein the formulation comprises three influenza virus strains.
20. A kit comprising the vaccine formulation of claim 18 and instructions.
21. A kit comprising the vaccine formulation of claim 19 and instructions.